(786e) Modulation of Lipid Composition As a Therapy in Alcohol Injured Liver Cells

Liver cells exposed to ethanol are altered in NADH/NAD⁺ ratio, generation of reactive oxygen species, excessive fat accumulation and cell apoptosis. These changes in a healthy liver can result in alcoholic liver diseases (ALDs), which are major causes of liver related morbidity in the world. However, despite the well documented metabolism of ethanol in parenchymal liver cells, hepatocytes, current treatment options are limited to cessation of alcohol consumption. Studies in other cell types and organisms have demonstrated that, in addition to changes in metabolism, physical changes to cell membranes occur upon exposure to ethanol and these changes are dependent on cell membrane lipid composition. Here we present an alternative perspective on mitigating ethanol injury on hepatocytes based on modulating the membrane lipid composition. Considering the likely relationship of lipid composition with ethanol tolerance from a yeast system, we use cationic liposomes that contain DOPC (1,2-dioleoyl- sn-glycero-3- phosphocholine) to recover the functionality of ethanol injured primary rat hepatocytes. As a cationic lipid, DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) is used to facilitate liposome cell interactions. Incorporation of the liposomes into the hepatocyte membranes were monitored by measuring DOTAP as a surrogate marker using liquid chromatography / mass spectrometry with a triple quadrupole (QqQ) mass analyzer and an electrospray ionization source (ESI). Cell function was assessed using secreted albumin as a marker. The results of these in vitro studies illustrate the potential of using cationic liposomes to mitigate ethanol injury in vivo using existing or novel means of delivering lipids to hepatocytes in the liver.